Epithelial Fluid Transport is Due to Electro-osmosis (80%), Plus Osmosis (20%).

Epithelial fluid transport, an important physiological process shrouded in a long-standing enigma, may finally be moving closer to a solution. We propose that, for the corneal endothelium, relative proportions for the driving forces for fluid transport are 80% of paracellular electro-osmosis, and 20% classical transcellular osmosis. These operate in a cyclical process with a period of 9.2 s, which is dictated by the decrease and exhaustion of cellular Na+. Paracellular electro-osmosis is sketched here, and partially discussed as much as the subject still allows; transcellular osmosis is presented at length.

Balance of unidirectional monovalent ion fluxes in cells undergoing apoptosis: why does Na+/K+ pump suppression not cause cell swelling?

Cells dying according to the apoptotic program, unlike cells dying via an unprogrammed mode, are able to avoid swelling and osmotic bursting with membrane disruption.There are indications that apoptosis is accompanied by suppression of the Na+/K+ pump and changes in the K+ and Cl− channels. It remains unclear how ion fluxes through individual ion pathways are integrated so as to induce loss of intracellular ions and concomitant apoptotic volume decrease. A decrease in activity of the sodium pump during apoptosis should cause cell swelling rather than shrinkage. We have made the first systemic analysis of the monovalent ion flux balance in apoptotic cells. Experimental data were obtained for human U937 cells treated with staurosporine for 4­5 h, which is known to induce apoptosis. The data include cellular Cl− content and fluxes, K+, Na+, water content and ouabain-sensitive and -resistant Rb+ fluxes.Unidirectional monovalent ion fluxeswere calculated using these data and a cell model comprising the double Donnan system with the Na+/K+ pump, Cl−, K+, Na+ channels, the Na+­K+­2Cl−cotransporter (NKCC), the Na+­Cl− cotransporter (NC), and the equivalent Cl−/Cl− exchange.Apoptotic cell shrinkage was found to be caused, depending on conditions, either by an increase in the integral channel permeability of membrane for K+ or by suppression of the pump coupledwith a decrease in the integral channel permeability of membrane for Na+. The decrease in the channel permeability of membrane for Na+ plays a crucial role in cell dehydration in apoptosis accompanied by suppression of the pump. Supplemental Table S1 is given for easy calculating flux balance under specified conditions.

Pump and channel K (Rb+) fluxes in apoptosis of human lymphoid cell line U937.

Ouabain-sensitive (OS) and -resistant (OR) Rb(+) influx was examined in three sublines of U937 cells to compare alterations of K(+) channel permeability and the Na(+),K(+)-ATPase pump leading to the shift in ion and water balance during apoptosis induced by 0.2 and 1microM staurosporine (STS) for 4-5 h. Cell K(+), Rb(+), Na(+) and Cl(-) content was determined by flame photometry and (36)Cl distribution. Changes in cell water content were monitored by measurement of buoyant cell density and distribution of [(3)H]-glycerol or 3-O-methyl-D-[(3)H]glucose. Apoptosis was detected by DNA flow cytometry and light microscopy of the native cells stained with acridine orange. Treatment with 0.2 microM STS for 5 hours led to mild apoptosis with 10-13 % cell dehydration and either moderate increase of channel mediated Rb(+) influx without significant changes in the pump activity or moderate decrease of pump Rb(+) influx without significant change of channel influx, depending on the cell line used. Treatment with 1 microM STS was followed by 18-23 % cell dehydration, a decrease of the pump activity and a small or insignificant increase in the OR Rb(+) influx in all studied sublines. It is concluded that moderate apoptotic cell shrinkage may be associated with both an increase in K(+) channel permeability and inhibition of the pump whereas more remarkable shrinkage occurs presumably due to inhibition of the pump.